This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Parkinson's disease is a progressive neurodegenerative disorder that starts many years prior to the appearance of the first motor symptoms. Thus, if one could intervene early in the disease process to slow down or reverse the progressive degeneration of midbrain dopaminergic neurons, it could have a significant impact on the development of the disease. The goal of this project is to identify preclinical biomarkers that would give the opportunity to pre-treat at risk patients with neuroprotective therapeutic drugs, which could significantly delay or even prevent the death of dopaminergic neurons and the development of motor deficits. In collaboration with Dr Jing Zhang at the University of Washington, this project aims at identifying such biomarkers using proteomics approach from the serum, cerebrospinal fluid and brain tissue in MPTP-treated monkeys. Although no data have yet been collected in this project, a total of 10 monkeys have been treated with MPTP until they reach about 30-40% ("asymptomatic group") or 70-80% ("symptomatic group") striatal dopamine loss, as measured using PET scan imaging for dopamine transporter ligands. Another group of animals, used as controls, was injected with vehicle. After they have reached the required level of striatal dopamine denervation, spinal taps and serum draw were performed before the animals were sacrificed and the brain tissue will be used for proteomics measurements. The results of these monkey studies will be compared with those gathered from serum and CSF measurements collected from at risk patients. Together, these findings could provide the first evidence for the characterization of biomarkers that could predict the development of Parkinson's disease in humans.